细胞外信号调节激酶信号通路与基质金属蛋白酶-26在肺腺癌表达中的关系

Correlation of extracellular signal-regulated kinase signal transduction pathway with MMP-26 expression in lung adenocarcinoma

目的研究细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)通路与基质金属蛋白酶-26(matrix metalloproteinase-26,MMP-26)在肺腺癌表达的相关性及意义。方法应用免疫组织化学(S-P)法检测pERK、pp38MAPK及MMP-26在44例肺腺癌组织中的表达。Western blot检测U0126阻断ERK信号通路后肺腺癌A549细胞MMP-26蛋白表达水平的变化。分析pERK和MMP-26表达与肺腺癌预后的关系。结果pERK、pp38MAPK及MMP-26蛋白在肺腺癌组织中高表达率分别为59.1%、20.4%、54.5%,pERK与MMP-26表达存在正相关(r=0.63,P<0.05),并与肺腺癌的临床分期及淋巴转移状况有统计学差异(P<0.05),而与患者年龄、肿瘤大小无统计学差异(P>0.05)。pp38MAPK与MMP-26表达无关(r=0.01,P>0.05),与患者年龄、淋巴转移、肿瘤大小、临床分期均无统计学差异(P>0.05)。用ERK阻断剂U0126阻断ERK信号通路可降低MMP-26蛋白表达水平,并且随U0126浓度升高MMP-26蛋白表达水平逐渐降低。肺腺癌组织pERK、MMP-26蛋白的表达与肿瘤的预后显著相关(分别为Log-Rank=5.52、Log-Rank=7.01,P=0.019、P=0.008)。结论ERK信号通路可能通过上调MMP-26的表达促进肺腺癌的恶性进展,ERK信号通路可能是肺腺癌侵袭和转移的重要途径,pERK和MMP-26的表达可辅助用于肺腺癌的预后评估。

Objective To investigate the correlation of extracellular signal-regulated kinase （ERK） with matrix metalloproteinase-26 （MMP-26） and its significance in lung adenocarcinoma. Methods SP immunohistochemistry was used to test the expressions of pERK, pp38MAPK and MMP-26 in 44 specimens of lung adenocarcinoma. Western blotting was used to detect the protein levels of MMP-26 in A549 cells after blocking ERK signal transduction pathway with U0126. The correlation of pERK and MMP-26 expressions with prognosis of lung adenocarcinoma was analyzed. Results The positive rates of pERK, pp38MAPK and MMP-26 proteins in lung adenocarcinoma tissues were 59.1% , 20.4% and 54.5%, respectively. The expression of pERK was positively correlated to the expression of MMP-26 （r = 0.63, P 〈 0.05 ） , and the expression of pp38MAPK was not related to MMP-26 expression （ r = 0. 01, P 〉 0. 05 ）. The expression of pERK was correlated to lymph node metastasis and TNM stage （P 〈0.05）, but not to age and tumor size （P 〉0.05）. pp38MAPK was not correlated to age, lymph node metastasis, tumor size or TNM stage （P 〉0. 05 ）. U0126 concentration-dependently inhibited ERK pathway and reduced MMP-26 protein expression. The expressions of pERK and MMP-26 were negatively correlated to prognosis of lung adenocarcinoma （ Log-Rank = 5.52, 7.01 ; P = 0. 019, 0. 008 ）.Conclusion ERK signal transduction pathway might promote lung adenocarcinoma progression by up-regulating MMP-26 expression, and might be an important route in invasion and metastasis of lung adenocarcinoma. pERK and MMP-26 expressions might help make prognosis of lung adenocarcinoma.